• K Simmer, S K Patole, and S C Rao.
• King Edward Memorial Hospital for Women and Princess Margaret Hospital for Children, Neonatal Clinical Care Unit, Bagot Road, Subiaco, WA, Australia 6008. Karen.Simmer@health.wa.gov.au
• Cochrane Db Syst Rev. 2008 Jan 23 (1): CD000376.

BackgroundThe n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Controversy exists over whether LCPUFA are also essential nutrients in infancy. Over the last few years, some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants.ObjectivesTo assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants.Search StrategyEligible studies were identified by searching MEDLINE (March 2007), EMBASE 1980 - 2007, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and CINAHL (December 1982 - March 2007). Abstracts of the Society for Pediatric Research were hand searched from 1980 to 2006 inclusive. Reference lists of published narrative and systematic reviews were also reviewed. No language restrictions were applied.Selection CriteriaAll randomised and quasi randomised trials comparing LCPUFA supplemented formula milk vs. non-supplemented formula milk and with clinical endpoints were reviewed.Data Collection And AnalysisMethodological quality of eligible studies was assessed according to allocation concealment, blinding of intervention, blinding of outcome assessment and completeness of follow up. Data were sought regarding effects on visual acuity, neurodevelopmental outcomes and physical growth. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. Continuous data were analysed using weighted mean difference (WMD). There were no categorical outcomes in this review.Main ResultsTwenty randomised studies were identified. Fourteen were included (n = 1719) and six excluded. Eleven included studies were of good quality. The main outcomes assessed were visual acuity, neurodevelopmental and physical growth. Visual acuity was measured at various stages throughout the first three years of life by nine studies. Visual evoked potential was used to assess visual acuity in five studies. The remaining four used Teller visual acuity cards. The results were inconsistent. Three studies reported beneficial effect of LCPUFA supplementation on visual acuity while the remaining six did not. Neurodevelopmental outcome was measured at different ages throughout the first two years by eleven studies. Bayley scales of infant development (BSID) was used in eight studies. Only one showed beneficial effect of LCPUFA supplementation on BSID scales. Pooled meta-analysis of the data also did not show any statistically significant benefit of LCPUFA supplementation on either mental or psychomotor developmental index of BSID. One study reported better novelty preference measured by Fagan Infant test at nine months in supplemented infants compared with controls. Another study reported better problem solving at 10 months with supplementation. One study used Brunet and Lezine developmental test to assess the developmental quotient and did not find beneficial effects of LCPUFA supplementation. Physical growth was measured at various ages throughout first three years of life by twelve studies. Some studies reported the actual measurements while some reported the rate of growth over a time period. Some studies z scores. Irrespective of the type of LCPUFA supplementation, duration of supplementation and method of assessment, none of the individual studies found beneficial or harmful effects of LCPUFA supplementation. Meta-analysis of relevant studies also did not show any effect of LCPUFA supplementation on growth of term infants.Authors' ConclusionsThe results of most of the well conducted RCTS have not shown beneficial effects of LCPUFA supplementation of formula milk on the physical, visual and neurodevelopmental outcomes of infants born at term. Only one group of researchers have shown some beneficial effects on VEP acuity. Two groups of researchers have shown some beneficial effect on mental development. Routine supplementation of milk formula with LCPUFA to improve the physical, neurodevelopmental or visual outcomes of infants born at term can not be recommended based on the current evidence. Further research is needed to see if the beneficial effects demonstrated by Dallas 2005 trial of Birch et al can be replicated in different settings.

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